Evidence map›Paper›PMID 37816000›Full record

Trial reportPloS one2023

Serum metabolomics of treatment response in myasthenia gravis.

Patricia Sikorski, Yaoxiang Li, Mehar Cheema, Gil I Wolfe, Linda L Kusner, Inmaculada Aban, Henry J Kaminski

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Myasthenia gravis: the future is here.The Journal of clinical investigation · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Patricia SikorskiDepartment of Neurology & Rehabilitation Medicine, George Washington University, Washington, DC, United States of America.
Yaoxiang LiDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States of America.ORCID 0000-0001-9200-1016
Mehar CheemaDepartment of Neurology & Rehabilitation Medicine, George Washington University, Washington, DC, United States of America.
Gil I WolfeDepartment of Neurology, University at Buffalo/SUNY, Buffalo, New York, United States of America.
Linda L KusnerDepartment of Pharmacology & Physiology, George Washington University, Washington, DC, United States of America.ORCID 0000-0002-5530-2140
Inmaculada AbanDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Henry J KaminskiDepartment of Neurology & Rehabilitation Medicine, George Washington University, Washington, DC, United States of America.ORCID 0000-0002-8195-0141
George Washington University · USGeorgetown University · USUniversity at Buffalo, State University of New York · USUniversity of Alabama at Birmingham · US

Funding

Rare Disease Network for Myasthenia GravisU54NS115054 · NINDS · GEORGE WASHINGTON UNIVERSITY · PI Linda Louise Kusner · 2019 to 2026
$11.9M
Thymectomy in Non-Thymomatous MG Patients on PrednisoneU01NS042685 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUTTER, GARY R · 2005 to 2015
$11.7M
NINDS NIH HHS U01 NS042685NINDS NIH HHS U54 NS115054
6 · The paper itself

Abstract

objectiveHigh-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone.

methodsWe applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response.

resultsIncreased serum levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90 irrespective of gender, age, thymectomy or baseline prednisone use. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. There was no association with outcome and gender, age, thymectomy or baseline prednisone use.

interpretationWe have defined a metabolomic and lipidomic profile that can now undergo validation as a treatment predictive marker for MG patients undergoing corticosteroid therapy. Metabolomic profiles of outcome measures had limited overlap consistent with their assessing distinct aspects of treatment response and supporting unique biological underpinning for each outcome measure. Interindividual variation in prednisone metabolism may be a determinate of how well patients respond to treatment.

Indexed as

Activities of Daily LivingMyasthenia GravisCombined Modality TherapyGlucocorticoidsHumansPrednisoneThymectomyTreatment OutcomeGlucocorticoidsPrednisone

Identifiers

PMID37816000
PMCPMC10564178
OpenAlexW4387493166

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.